Sex and Tamoxifen confound murine experimental studies in cardiovascular tissue engineering

Abstract Tissue engineered vascular grafts hold promise for the creation of functional blood vessels from biodegradable scaffolds. Because the precise mechanisms regulating this process are still under investigation, inducible genetic mouse models are an important and widely used research tool. Howe...

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Autores principales:	Kevin M. Blum, Lauren C. Roby, Jacob C. Zbinden, Yu-Chun Chang, Gabriel J. M. Mirhaidari, James W. Reinhardt, Tai Yi, Jenny C. Barker, Christopher K. Breuer
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e7de3cbd0e39491ab82f2557cb8e8c1f
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spelling	oai:doaj.org-article:e7de3cbd0e39491ab82f2557cb8e8c1f2021-12-02T14:26:16ZSex and Tamoxifen confound murine experimental studies in cardiovascular tissue engineering10.1038/s41598-021-87006-32045-2322https://doaj.org/article/e7de3cbd0e39491ab82f2557cb8e8c1f2021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-87006-3https://doaj.org/toc/2045-2322Abstract Tissue engineered vascular grafts hold promise for the creation of functional blood vessels from biodegradable scaffolds. Because the precise mechanisms regulating this process are still under investigation, inducible genetic mouse models are an important and widely used research tool. However, here we describe the importance of challenging the baseline assumption that tamoxifen is inert when used as a small molecule inducer in the context of cardiovascular tissue engineering. Employing a standard inferior vena cava vascular interposition graft model in C57BL/6 mice, we discovered differences in the immunologic response between control and tamoxifen-treated animals, including occlusion rate, macrophage infiltration and phenotype, the extent of foreign body giant cell development, and collagen deposition. Further, differences were noted between untreated males and females. Our findings demonstrate that the host-response to materials commonly used in cardiovascular tissue engineering is sex-specific and critically impacted by exposure to tamoxifen, necessitating careful model selection and interpretation of results.Kevin M. BlumLauren C. RobyJacob C. ZbindenYu-Chun ChangGabriel J. M. MirhaidariJames W. ReinhardtTai YiJenny C. BarkerChristopher K. BreuerNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Kevin M. Blum Lauren C. Roby Jacob C. Zbinden Yu-Chun Chang Gabriel J. M. Mirhaidari James W. Reinhardt Tai Yi Jenny C. Barker Christopher K. Breuer Sex and Tamoxifen confound murine experimental studies in cardiovascular tissue engineering
description	Abstract Tissue engineered vascular grafts hold promise for the creation of functional blood vessels from biodegradable scaffolds. Because the precise mechanisms regulating this process are still under investigation, inducible genetic mouse models are an important and widely used research tool. However, here we describe the importance of challenging the baseline assumption that tamoxifen is inert when used as a small molecule inducer in the context of cardiovascular tissue engineering. Employing a standard inferior vena cava vascular interposition graft model in C57BL/6 mice, we discovered differences in the immunologic response between control and tamoxifen-treated animals, including occlusion rate, macrophage infiltration and phenotype, the extent of foreign body giant cell development, and collagen deposition. Further, differences were noted between untreated males and females. Our findings demonstrate that the host-response to materials commonly used in cardiovascular tissue engineering is sex-specific and critically impacted by exposure to tamoxifen, necessitating careful model selection and interpretation of results.
format	article
author	Kevin M. Blum Lauren C. Roby Jacob C. Zbinden Yu-Chun Chang Gabriel J. M. Mirhaidari James W. Reinhardt Tai Yi Jenny C. Barker Christopher K. Breuer
author_facet	Kevin M. Blum Lauren C. Roby Jacob C. Zbinden Yu-Chun Chang Gabriel J. M. Mirhaidari James W. Reinhardt Tai Yi Jenny C. Barker Christopher K. Breuer
author_sort	Kevin M. Blum
title	Sex and Tamoxifen confound murine experimental studies in cardiovascular tissue engineering
title_short	Sex and Tamoxifen confound murine experimental studies in cardiovascular tissue engineering
title_full	Sex and Tamoxifen confound murine experimental studies in cardiovascular tissue engineering
title_fullStr	Sex and Tamoxifen confound murine experimental studies in cardiovascular tissue engineering
title_full_unstemmed	Sex and Tamoxifen confound murine experimental studies in cardiovascular tissue engineering
title_sort	sex and tamoxifen confound murine experimental studies in cardiovascular tissue engineering
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/e7de3cbd0e39491ab82f2557cb8e8c1f
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_version_	1718391402653548544

Sex and Tamoxifen confound murine experimental studies in cardiovascular tissue engineering

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